Genotyping and Phylogenetic Analysis of Yersinia pestis by MLVA: Insights into the Worldwide Expansion of Central Asia Plague Foci

BACKGROUND: The species Yersinia pestis is commonly divided into three classical biovars, Antiqua, Medievalis, and Orientalis, belonging to subspecies pestis pathogenic for human and the (atypical) non-human pathogenic biovar Microtus (alias Pestoides) including several non-pestis subspecies. Recent progress in molecular typing methods enables large-scale investigations in the population structure of this species. It is now possible to test hypotheses about its evolution which were proposed decades ago. For instance the three classical biovars of different geographical distributions were suggested to originate from Central Asia. Most investigations so far have focused on the typical pestis subspecies representatives found outside of China, whereas the understanding of the emergence of this human pathogen requires the investigation of strains belonging to subspecies pestis from China and to the Microtus biovar. METHODOLOGY/PRINCIPAL FINDINGS: Multi-locus VNTR analysis (MLVA) with 25 loci was performed on a collection of Y. pestis isolates originating from the majority of the known foci worldwide and including typical rhamnose-negative subspecies pestis as well as rhamnose-positive subspecies pestis and biovar Microtus. More than 500 isolates from China, the Former Soviet Union (FSU), Mongolia and a number of other foci around the world were characterized and resolved into 350 different genotypes. The data revealed very close relationships existing between some isolates from widely separated foci as well as very high diversity which can conversely be observed between nearby foci. CONCLUSIONS/SIGNIFICANCE: The results obtained are in full agreement with the view that the Y. pestis subsp. pestis pathogenic for humans emerged in the Central Asia region between China, Kazakhstan, Russia and Mongolia, only three clones of which spread out of Central Asia. The relationships among the strains in China, Central Asia and the rest of the world based on the MLVA25 assay provide an unprecedented view on the expansion and microevolution of Y. pestis

Prolonged repolarization in the early phase of ischemia is associated with ventricular fibrillation development in a porcine model

Background: Repolarization prolongation can be the earliest electrophysiological change in ischemia, but its role in arrhythmogenesis is unclear. The aim of the present study was to evaluate the early ischemic action potential duration (APD) prolongation concerning its causes, expression in ECG and association with early ischemic ventricular fibrillation (phase 1A VF).Methods: Coronary occlusion was induced in 18 anesthetized pigs, and standard 12 lead ECG along with epicardial electrograms were recorded. Local activation time (AT), end of repolarization time (RT), and activation-repolarization interval (ARIc) were determined as dV/dt minimum during QRS-complex, dV/dt maximum during T-wave, and rate-corrected RT–AT differences, respectively. Patch-clamp studies were done in enzymatically isolated porcine cardiomyocytes. IK(ATP) activation and Ito1 inhibition were tested as possible causes of the APD change.Results: During the initial period of ischemia, a total of 11 pigs demonstrated maximal ARIc prolongation >10 ms at 1 and/or 2.5 min of occlusion (8 and 6 cases at 1 and 2.5 min, respectively) followed by typical ischemic ARIc shortening. The maximal ARIc across all leads was associated with VF development (OR 1.024 95% CI 1.003–1.046, p = 0.025) and maximal rate-corrected QT interval (QTc) (B 0.562 95% CI 0.346–0.775, p < 0.001) in logistic and linear regression analyses, respectively. Phase 1A VF incidence was associated with maximal QTc at the 2.5 min of occlusion in ROC curve analysis (AUC 0.867, p = 0.028) with optimal cut-off 456 ms (sensitivity 1.00, specificity 0.778). The pigs having maximal QTc at 2.5 min more and less than 450 ms significantly differed in phase 1A VF incidence in Kaplan-Meier analysis (log-rank p = 0.007). In the patch-clamp experiments, 4-aminopyridine did not produce any effects on the APD; however, pinacidil activated IK(ATP) and caused a biphasic change in the APD with initial prolongation and subsequent shortening.Conclusion: The transiently prolonged repolarization during the initial period of acute ischemia was expressed in the prolongation of the maximal QTc interval in the body surface ECG and was associated with phase 1A VF. IK(ATP) activation in the isolated cardiomyocytes reproduced the biphasic repolarization dynamics observed in vivo, which suggests the probable role of IK(ATP) in early ischemic arrhythmogenesis

Insight into Microevolution of Yersinia pestis by Clustered Regularly Interspaced Short Palindromic Repeats

BACKGROUND: Yersinia pestis, the pathogen of plague, has greatly influenced human history on a global scale. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), an element participating in immunity against phages' invasion, is composed of short repeated sequences separated by unique spacers and provides the basis of the spoligotyping technology. In the present research, three CRISPR loci were analyzed in 125 strains of Y. pestis from 26 natural plague foci of China, the former Soviet Union and Mongolia were analyzed, for validating CRISPR-based genotyping method and better understanding adaptive microevolution of Y. pestis. METHODOLOGY/PRINCIPAL FINDINGS: Using PCR amplification, sequencing and online data processing, a high degree of genetic diversity was revealed in all three CRISPR elements. The distribution of spacers and their arrays in Y. pestis strains is strongly region and focus-specific, allowing the construction of a hypothetic evolutionary model of Y. pestis. This model suggests transmission route of microtus strains that encircled Takla Makan Desert and ZhunGer Basin. Starting from Tadjikistan, one branch passed through the Kunlun Mountains, and moved to the Qinghai-Tibet Plateau. Another branch went north via the Pamirs Plateau, the Tianshan Mountains, the Altai Mountains and the Inner Mongolian Plateau. Other Y. pestis lineages might be originated from certain areas along those routes. CONCLUSIONS/SIGNIFICANCE: CRISPR can provide important information for genotyping and evolutionary research of bacteria, which will help to trace the source of outbreaks. The resulting data will make possible the development of very low cost and high-resolution assays for the systematic typing of any new isolate

Introducing a New Detailed Long-Term COSMO-CLM Hindcast for the Russian Arctic and the First Results of Its Evaluation

Diverse and severe weather conditions and rapid climate change rates in the Arctic emphasize the need for high-resolution climatic and environmental data that cannot be obtained from the scarce observational networks. This study presents a new detailed hydrometeorological dataset for the Russian Arctic region, obtained as a long-term hindcast with the nonhydrostatic atmospheric model COSMO-CLM for the 1980–2016 period. The modeling workflow, evaluation techniques, and preliminary analysis of the obtained dataset are discussed. The model domain included the Barents, Kara, and Laptev Seas with ≈12-km grid spacing. The optimal model setup was chosen based on preliminary simulations for several summer and winter periods with varied options, and included the usage of ERA-Interim reanalysis data as forcing data, the new model version 5.05 with so-called ICON-based physics, and a spectral nudging technique. The wind speed and temperature climatology in the new COSMO-CLM dataset closely agreed with the ERA-Interim reanalysis, but with detailed spatial patterns. The added value of the higher-resolution COSMO-CLM data with respect to the ERA-Interim was most pronounced for higher wind speeds during downslope windstorms with the influence of mountain ranges on the temperature patterns, including surface temperature inversions. The potential applications and plans of further product development are also discussed

Arctic COSMO-CLM hindcast 2017

Russian Arctic COSMO-CLM hindcast 2017</p

Arctic COSMO-CLM hindcast 2009

Russian Arctic COSMO-CLM hindcast 2009</p

Megacity-Induced Mesoclimatic Effects in the Lower Atmosphere: A Modeling Study for Multiple Summers over Moscow, Russia

Urbanization leads to distinct meteorological features of urban environments, and one the best-known is the urban heat island (UHI) effect. For megacities, these features become mesoscale phenomena (scale ≥ 10 km) that are amplified by the tropospheric feedbacks, and have substantial implications on human well-being. For the first time, a three-dimensional statistical description of the megacity-induced meteorological effects extending towards the lower troposphere for summer is acquired on a quasi-climatological timescale (a decade) based on high-resolution (1 km) simulations for Moscow with the COSMO-CLM model with and without its urban canopy model TERRA_URB. Our results confirm the features from previous observational and modeling studies, including the UHI itself, the cooling effect above established by the cross-over effect, the urban dry/moist islands and the urban breeze circulation. Particularly, the UHI shows a strong diurnal variation in terms of intensity and vertical extent between daytime (≈0.5 K/≈1.5 km) and nighttime (&gt;3 K/≈150 m). We have discovered a systematic veering in the downwind shift of the UHI spatial pattern established by the Coriolis effect, and an enhanced stable stratification of the rural surroundings established by the urban plumes further downwind. Finally, extending the analysis to multiple summers demonstrates a substantial increase in summer precipitation (up to +25%) over the city center and its leeward side. These urban-caused mesoclimatic effects need to be taken into account in weather and climate services, including the design of future megacities

Investigation of urban-induced mesoclimatic anomalies in the lower atmosphere over Moscow megacity based on simulations with COSMO-CLM model for multiple summers

status: publishe

КИСЛОРОДНОЕ ОБЕСПЕЧЕНИЕ ОРГАНИЗМА СПОРТСМЕНОВ ПРИ НАГРУЗКАХ МАКСИМАЛЬНОЙ ИНТЕНСИВНОСТИ

Mechanism of oxygen supply have been studied in sportsmen - athletes sprinters and middle-distance runners at maximal physical exercises. Found heat the sportsmen, specializing in middle-distance race as distinct from qualified sprinter have higher spare capacities of external respiration, blood, cardiovascular system and cell respiration hat determine a high lever of his aerobic capacity.Изучены механизмы кислородного обеспечения организма спортсменов - легкоатлетов, бегунов на короткие и средние дистанции в при работе максимальной мощности. Установлено, что в отличие от квалифицированных «спринтеров» спортсмены, специализирующиеся в беге на средние дистанции имеют более высокие резервные возможности внешнего дыхания, крови, сердечно-сосудистой системы и тканевого дыхания, определяющие высокий уровень их аэробной работоспособности